Lateral olivocochlear (LOG) efferent endings on Type I auditory nerve (AN) peripheral processes are strategically placed to provide a powerful and dynamic regulation of AN activity. We have developed methods to lesion the LOG which allowed our lab and others to show changes in auditory evoked potential (CAP, ABR) amplitudes that could specifically be attributed to the loss of LOG innervation. This has led us to hypothesize that the LOG acts on auditory nerve peripheral processes to increase dynamic range across AN fibers, which in turn has the function of improving intensity discrimination. Our proposed specific aims test this hypothesis using MPTP to transiently disrupt LOG processes in the cochlea, without disrupting afferents or the central auditory pathways. Specific Aim 1 uses electron microscopy, immunocytochemistry and whole nerve recording to test the hypothesis that LOG disruption by MPTP will (H1a) induce a transient LOG specific loss of fibers and terminals whose loss will (H1b) result in decreases in AN spontaneous activity, adaptation and dynamic range. (H1c) A greater morphological disruption will correlate with more effect on AN responses. Specific Aim 2 is based on preliminary results that show that when LOG efferents co-contain both DA and other neurotransmitters, immunolabeling for both decreases following MPTP application. This leads us to hypothesize (H2) that dopamine and other LOG transmitters can be "co-disrupted" by MPTP when they are co-contained in the same fiber, including disruption of neurotransmitters believed to be excitatory. Specific Aim 3 uses single unit AN recording to test the hypothesis that disruption of the LOG innervation of the cochlea will (H3a) suppress spontaneous AN activity, (H3b) alter sound-induced responses of AN, and (H3c) reduce tonic adaptation of AN, resulting in a "redistribution" of the proportion of High (H), Medium (M) and Low (L) spontaneous rate (SR) fibers Specific Aim 4 uses behavioral psychophysics to test the hypotheses that MPTP-induced disruption of LOG efferents will (H4a) alter dynamic range for perceived loudness of signals and (H4b) decrease acuity for intensity-related psychophysical discrimination tasks. (H4c) MPTP will have no effect on frequency discrimination These studies will increase our knowledge of mechanisms of LOG action at the first synaptic complex in the cochlea. They will test the LOG contribution to loudness perception and intensity discrimination. As such there will be clinical relevance towards interventions to protect AN from excitotoxic injury (from noise) and treatment of "cocktail party syndrome" and similar processing disorders, where the LOG may play an important role in detecting signals in a noisy background. [unreadable] [unreadable] [unreadable]